Suspensions or slurries having moderate and high particle concentrations are found in a variety of industries such as chemical and pharmaceutical manufacturing and waste remediation. As the characteristics of the suspensions have considerable influence on production costs, product quality and yield, there is a continual need to rapidly, cost-effectively, and non-invasively characterize these suspensions in real time. The present invention is generally directed to addressing this need.
In particular, a variety of industrial processes rely on the biological functioning of cells. For example, industrial scale fermentation processes are encountered in various pharmaceutical and chemical industries, and typically involve fungi, bacteria, or mammalian cells that biologically convert raw materials (nutrient broth) into a desired product. Examples are ethanol fermentation using yeast, human insulin production using bacteria or yeast, and human Factor VIII using mammalian cells. While the individual cells are typically tailored to produce a specific product under controlled conditions, there is a need to know the fermentation conditions, such as the number of cells per volume, their size and size distribution, and the fraction of cells that are alive (i.e. cell viability) in order to ensure accurate control and reproducibility. Past efforts at monitoring the cells during industrial fermentation has required physical extraction of samples from the fermentor and off-line processing, such as optical density (absorption) measurements. Not only is the withdrawal of a sample from a fermentor time consuming and potentially disruptive, but optical density measurements are generally only effective over a narrow region of cell concentration. Therefore, additional sample preparation, such as dilution, is often required to achieve proper characterization, increasing the potential for error, cost, and complexity of process monitoring. Accordingly, improvements are needed, and in one or more embodiments, the present invention addresses these and other concerns.